Anna Martling, MD, PhD, on the ALASCCA Trial in Colorectal Cancer

At this year's ASCO GI in San Francisco, I will present the data from the ALASCCA trial, which is the first biomarker-driven randomized control trial studying the potential effect of adjuvant low-dose aspirin to patients with colorectal cancer using a predictive biomarker. Colorectal cancer is one of the most common cancer diagnoses in the world. Around 2 million people each year get a diagnosis of colorectal cancer. And despite advancements in new treatment strategies, new diagnostic methods, it's still the second leading cause of cancer death. So there is a unmet need, a large unmet need, to improve both diagnostics, gaining new biomarkers, but also a new treatment strategies. Aspirin, the drug used in this trial, is perhaps one of the most well-known, well-proven drugs on the market. It has been on the market for over 120 years. And already a thousand years ago, people ate shoot white willow bark that contains acetyl salicylic acid for pain-killing effects. And it has been used on the market since 120 years, as I said, mostly for pain-killing effects, but also for fever reduction and later on in the cardiovascular field. But it's also known, and that is from observational studies in the cardiovascular field, that people being on aspirin from other causes do have a lower risk of getting colorectal cancer. And it has also been shown to risk groups in patients having a high risk of getting polyps in the bowel and getting colorectal cancer that low-dose aspirin reduces the risk of getting polyps in the bowel but also the risk of getting colorectal cancer. The results from the trial shows that the primary endpoint was met. Aspirin significantly reduced the risk of recurrence of patients with PIK3CA mutations compared to placebo. Specifically, patients receiving aspirin had a 51% lower risk of recurrence compared to patients on placebo, with a recurrence rate of 7.7 of those taking aspirin compared to 14.1% in the placebo group. Interesting, also in the exploratory arm, outside the hotspot regions, the effect was even stronger with a 50% reduction in recurrence. So this finding considerably expand the target patient population to almost 40% of all patients with early colorectal cancer. The trial was not originally powered for subgroup analysis, however, the results were very consistent. No matter mutation, the effect was in both colon and rectal cancer. It was in those getting neoadjuvant or adjuvant treatment or not getting adjuvant treatment, both in stage two and three disease and in both sexes, but with a stronger effect in females. Aspirin is a well proven drug, as I said, and we know almost all side effects. The incidence of adverse events in the study was very low and severe side effects associated with daily low-dose aspirin were rare. So to conclude, aspirin 160 milligram daily, inpatient with PIK3CA mutation reduce the risk of recurrence by more than 50% compared to placebo. And this is the first trial to show that also other mutations in the same signal pathway, beyond the PIK3CA, predicts aspirin respond, expanding the population to almost 40% that could gain on aspirin. And this is an example of precision medicine also repurposing a drug, how high technology platforms new diagnosis can be used to explore the effect of drugs already available on the market. And it also stresses, of course, the important of genetic testing upfront.